Clinical TrialObsessive-Compulsive Disorder (OCD)MDMAPsilocybinNot yet recruiting

Developing Optimal Psychedelic Assisted Psychotherapy for Obsessive-Compulsive Disorder

This interventional randomised, blinded, parallel Phase II trial (n=40) compares MDMA-assisted psychotherapy (3 × 100 mg oral sessions) to psilocybin-assisted psychotherapy (3 × 25 mg oral sessions) for treatment-resistant OCD, with preparatory and integration therapy.

Target Enrollment
40 participants
Study Type
Phase II interventional
Design
Randomized, single Blind

Detailed Description

Randomised, blinded, parallel Phase II study enrolling 40 participants with treatment‑resistant obsessive‑compulsive disorder to compare MDMA‑assisted psychotherapy and psilocybin‑assisted psychotherapy, each delivered as three single‑dose medication sessions with structured psychological support.

Each medication arm includes a minimum of two 90‑minute preparation sessions, three medication sessions (up to 8 hours each, 2–6 weeks apart) and four 90‑minute integration sessions; therapists are trained health professionals and adherence is recorded electronically.

A subset of participants will undergo EEG at baseline and after the first and third drug sessions where equipment is available. Primary outcome includes change in Yale‑Brown Obsessive Compulsive Scale (YBOCS) scores; other measures include depression scales and follow‑up at 1, 3 and 6 months post‑integration.

Study Protocol

Preparation

2 sessions
90 min each

Dosing

3 sessions
480 min each

Integration

4 sessions
90 min each

Therapeutic Protocol

act

Study Arms & Interventions

MDMA + psychotherapy

experimental

Three single-dose MDMA-assisted psychotherapy sessions (2–6 weeks apart) with preparatory and integration therapy.

Interventions

  • MDMA100 mg
    via Oral• three sessions• 3 doses total

    Single 100 mg oral capsule administered by medical practitioner; sessions 2–6 weeks apart.

Psilocybin + psychotherapy

active comparator

Three single-dose psilocybin-assisted psychotherapy sessions (2–6 weeks apart) adapted from Yale manual, with preparatory and integration therapy.

Interventions

  • Psilocybin25 mg
    via Oral• three sessions• 3 doses total

    Single 25 mg oral capsule administered by medical practitioner; sessions 2–6 weeks apart.

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • Diagnosis of Obsessive-Compulsive Disorder, in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5)
  • 18-65 years of age.
  • Treatment resistant symptoms: For OCD: failure to tolerate or respond to at least 2 trials of adequate medication therapy (SSRI or clomipramine) at minimum effective therapeutic dose for at least 8 weeks
  • Moderate - severe symptoms: For OCD: YBOCS score of >13
  • Demonstrated capacity to give informed consent
  • Willingness and capacity (as judged on assessment by study clinicians) to engage in the therapeutic elements of the study protocol

Exclusion Criteria

  • Participants who are not able to give adequate informed consent.
  • Current or previously diagnosed psychotic disorder, schizophrenia or bipolar disorder
  • Immediate family member with a diagnosed psychotic disorder
  • Significant history of mania.
  • Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure)
  • History of serious suicide attempts in recent years requiring hospitalisation as judged by a study psychiatrist at initial assessment to impact on safety of participation.
  • Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin / MDMA, e.g., borderline personality disorder
  • Positive pregnancy test at screening or during the study, women who are planning a pregnancy and/or women who are nursing/breastfeeding.
  • Participants who do not agree to use an acceptable contraceptive method throughout their participation in the study.
  • Current drug or alcohol dependence
  • Recreational use in last 12 months of psychedelic substances or a history of regular psychedelic use
  • No email access/ability or no willingness to engage in follow up by electronic questionnaires
  • Use of contraindicated medication (outlined further below) including MAOI, SSRI or SNRI: SSRI/SNRI withdrawal for at least one week (4 weeks for fluoxetine), 2 weeks for irreversible MAOI
  • Use within 5 half-lives of any other serotonin-enhancing medication
  • Participants presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 440ms for men and above 470ms for women)
  • Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease.
  • Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
  • BMI <17 or >42
  • Participants with significant difficulties in English comprehension or communication.

Study Details

Locations

Unknown facility — Australia

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